Peroxisome proliferator-activated receptor (PPAR)-γ2 is an adipose tissue-specific nuclear hormone receptor that regulates adipocytes differentiation and fat metabolism through a complex program concerning gene expression. This transcription factor, which is coded by the PPARG gene, located at the 3p25 region of the genome, appears to play an important role in bodyweight regulation. There are several polymorphisms in this gene that modulate the PPAR-γ2 function, which could also be associated with body weight and obesity. The Pro12Ala substitution is the most studied polymorphism of the PPARG gene. In this article, studies of the Pro12Ala variant and its association with obesity, including observational epidemiologic studies, gene–gene and gene–environment interaction studies as well as trials with dietary interventions are reviewed.